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BIDMC Scientists Develop Antibody to Treat Traumatic Brain Injury

Bonnie PrescottBeth Israel Deaconess Medical Center staff

SEPTEMBER 01, 2015

Traumatic brain injuries (TBI) affect approximately 20 percent of the more
than two million troops who have deployed to Iraq and Afghanistan, and
brain injuries caused by repeat concussions affect many professional
athletes. TBI is known to be a risk factor for the development of both
Alzheimer’s disease and chronic traumatic encephalopathy (CTE),
debilitating neurodegenerative diseases for which there is no cure.

Researchers at Beth Israel Deaconess Medical Center (BIDMC) have published
a new study in the journal Nature that explains how TBI leads to
these two types of dementia, but have also developed a new antibody that
can be used to treat traumatic brain injury before it causes widespread
brain damage.

“The problem of TBI and concussions developing from repetitive sports
injuries among football players and other athletes has gotten a lot of
attention in recent years,” explains Dr. Kun Ping Lu, the Director of
Translational Therapeutics in the Department of Medicine at BIDMC.

These include the highly publicized case of the late National Football
League player Junior Seau, who committed suicide after developing CTE, a
degenerative brain disease associated with risk-taking, aggression and
depression — and ultimately progressive dementia.

The Tangled Brain

Dr. Lu and co-senior author Dr. Xiao Zhen Zhou have been investigating a
brain protein called tau. In healthy brains, the tau protein plays a key
role in memory and learning. But in Alzheimer’s and other neurodegenerative
diseases, tau can become misshapen and develop into tangles — and
subsequent disease.

“We found that the tau protein misfolds and turns into the misshapen cis P-tau, within as little as 12 hours following a traumatic
brain injury,” says Dr. Lu. If it is not stopped, the misshapen protein can
spread throughout the brain, destroying brain cells and leading to dementia
and other serious behavioral and psychological problems.

Dr. Zhou developed an antibody that can intervene to stop this process.
Known as a monoclonal antibody, this technology is popular drug development
approach that can be used therapeutically to both detect the misshapen
protein and then neutralize it so that it goes back to its normal shape.

“This antibody was shown in our animal models to stop the destructive
process of cisP-tau,” says Zhou. “The antibody can correct the
shape of the protein and turn it back into normal functioning tau.”

This research was conducted in animal models, but the scientists hope that
within two to three years, they will be able to develop an antibody therapy
that can be tested in humans in clinical trials. And this could conceivably
help to treat people after a car accident, military injury or repeated
concussions, enabling doctors to identify and treat problems at the very
early stages of disease.

"Alzheimer’s disease and chronic traumatic encephalopathy are terrible
diseases that progressively rob individuals of their memory, judgment and
ability to function,” says Lu. “We will continue to work to develop this
antibody in the hopes that one day this clinical treatment will be
available to prevent the long-term consequences of TBI in humans.”